title: Cytokine signatures of transformed B cells with distinct Epstein-Barr virus latencies as a potential diagnostic tool for B cell lymphoma.
abstract: Immunocompromised individuals, including those infected with human immunodeficiency virus (HIV), are at increased risk of Epstein-Barr virus (EBV)-associated aggressive B cell malignancies such as Burkitt's lymphoma (BL) or diffuse large B cell lymphoma (DLBCL). Differential diagnosis of these lymphomas requires histopathological, immunohistochemical and cytogenetic assessments. Rapid, less invasive approaches to the diagnosis of EBV-associated B cell lymphomas are needed. Here, high-throughput cytokine profiling of BL cell lines and EBV-transformed B lymphoblastoid cell lines (B-LCL), representing DLBCL, was carried out. By monitoring the production of 42 different cytokines, unique cytokine signatures were identified for BL and B-LCL/DLBCL. The BL cells produced interleukin (IL)-10, 10 kDa interferon gamma-induced protein (IP-10)/CXCL10, macrophage-derived chemokine (MDC)/CCL22, macrophage inflammatory protein (MIP)-1α/CCL3 and MIP-1β/CCL4. In addition to these five cytokines, the cytokine signature of B-LCL/DLBCL cells included IL-8/CXCL8, IL-13, platelet-derived growth factor (PDGF)-AA, and regulated upon activation, normal T cell expressed and secreted (RANTES)/CCL5. Epstein-Barr virus latency was responsible for the increased production of IL-10, MDC/CCL22 and MIP-1α/CCL3 in BL cells, suggesting that EBV-mediated BL-genesis involves these three cytokines. These results suggest that high-throughput cytokine profiling might be a valuable tool for the differential diagnosis and might deepen our understanding of the pathogenesis of EBV-associated B cell malignancies.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Miyauchi
authors.forename: Emiko
authors.initials: E
authors.lastname: Urano
authors.forename: Hironori
authors.initials: H
authors.lastname: Yoshiyama
authors.forename: Jun
authors.initials: J
authors.lastname: Komano
mesh_terms: D002051:Burkitt Lymphoma / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D016207:Cytokines / Q000096:biosynthesis*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D017735:Virus Latency
chemical_list: D016207:Cytokines